ABSTRACT
UNLABELLED: A recently developed multiparameter computer-aided expert system (TheMa) for guiding anticoagulation with phenprocoumon (PPC) was validated by a prospective investigation in 22 patients. The PPC-INR-response curve resulting from physician guided dosage was compared to INR values calculated by "twin calculation" from TheMa recommended dosage. Additionally, TheMa was used to predict the optimal time to perform surgery or invasive procedures after interruption of anticogulation therapy. RESULTS: Comparison of physician and TheMa guided anticoagulation showed almost identical accuracy by three quantitative measures: Polygon integration method (area around INR target) 616.17 vs. 607.86, INR hits in the target range 166 vs. 161, and TTR (time in therapeutic range) 63.91 vs. 62.40 %. After discontinuation of anticoagulation therapy, calculating the INR phase-out curve with TheMa INR prognosis of 1.8 was possible with a standard deviation of 0.50 ± 0.59 days. CONCLUSION: Guiding anticoagulation with TheMa was as accurate as Physician guided therapy. After interruption of anticoagulant therapy, TheMa may be used for calculating the optimal time performing operations or initiating bridging therapy.
Subject(s)
Drug Monitoring/methods , Drug Therapy, Computer-Assisted/methods , International Normalized Ratio/methods , Phenprocoumon/administration & dosage , Prothrombin Time/methods , Thrombosis/blood , Thrombosis/prevention & control , Administration, Oral , Aged , Anticoagulants/administration & dosage , Anticoagulants/blood , Blood Coagulation/drug effects , Female , Humans , Male , Middle Aged , Phenprocoumon/blood , Reproducibility of Results , Sensitivity and Specificity , Thrombosis/diagnosis , Treatment OutcomeABSTRACT
Oral anticoagulation using vitamin K antagonists has been established for over 50 years. Although it is highly effective in preventing thromboembolic incidents, its therapeutic control still remains problematic. Therefore, a computer-aided approach is recommended for deriving dosages. Up to now, the dosage is often based on the visual inspection of previous INR measurements, average weekly doses, and the INR target range. Statistical variations of measurement results and time-delayed effects of dosages, however, frequently result in the misinterpretation of data and suggest pseudo-trends. Treating physicians are not only responsible for determining the patient-specific maintenance dose, but must also respond to deviating INR values, overdosage or underdosage, initiate the oral anticoagulation therapy, and control the INR level in case of a new target range (bridging). Instructive examples are provided to illustrate the described difficulties. A computer-aided expert system is currently developed to ensure the therapeutic safety under the specified conditions. We present preliminary results from a study designed to validate mathematical models underlying such expert systems.
Subject(s)
Anticoagulants/therapeutic use , Phenprocoumon/therapeutic use , Administration, Oral , Anticoagulants/administration & dosage , Anticoagulants/metabolism , Dose-Response Relationship, Drug , Drug Therapy, Computer-Assisted/methods , Humans , International Normalized Ratio , Kinetics , Phenprocoumon/administration & dosage , Phenprocoumon/metabolism , SafetyABSTRACT
Plasticity of synaptic connections plays an important role in the temporal development of neural networks which are the basis of memory and behavior. The conditions for successful functional performance of these nerve nets have to be either guaranteed genetically or developed during ontogenesis. In the latter case, a general law of this development may be the successive compensation of disturbances. A compensation type algorithm is analyzed here that changes the connectivity of a given network such that deviations from each neuron's equilibrium state are reduced. The existence of compensated networks is proven, the convergence and stability of simulations are investigated, and implications for cognitive systems are discussed.
